5.5 Normocytic Anemias with Extravascular Hemolysis

Question 1

Sickle cell trait

-lab tests to diagnose

Answer 1

1. Screening test: metabisulfite screen
   - causes cells with any amount of HbS to sickle (+ in disease and trait)
2. confirmation: Hb electrophoresis
   - can detect presence and amount of HbS

Question 2

Sickle cell anemia

-complications due to vaso-occlusion (5)

Answer 2

1. dactylitis
2. autosplenectomy (infection from encapsulated bacteria–most common cause of death in children)
3. acute chest syndrome (most common cause of death in adults)
4. Pain crisis
5. Renal papillary necrosis

Question 2

Sickle cell anemia

-how is the kidney affected? how does this present?

Answer 2

-Renal papillary necrosis, from vaso-occlusion.

gross hematuria and proteinuria

Question 3

Hereditary spherocytosis

-medical emergency risk with what infection?

Answer 3

-increased risk of aplstic anemia from parvovirus B19 infection. (of erythroid precursors)

Question 4

Normocytic anemias with predominant extravascular hemolysis

list them (4)

Answer 4

1. hereditary spherocytosis
2. sickle cell anemia
3. hemoglobin C
4. Immune hemolytic anemia

Question 4

Hereditary spherocytosis

-clinical/lab findings

Answer 4

1. spherocytes (with loss of central pallor)
2. high RDW, high MCHC (mean corpuscular Hb concentration)–high concentration of Hb in spherocytes
3. extravascular hemolysis symptoms: splenomegaly, jaundice from unconjugated bilirubin, and increased risk for bilirubin gallstones
4. increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors.

Question 5

Sickle Cell anemia

• what is the mutation
• inheritance pattern

Answer 5

• Auto recessive.
• single aa change in beta globin chain. glutamic (hydrophilic) to valine (hydrophobic)

Question 6

Hereditary spherocytosis

-what test to diagnose?

Answer 6

• osmotic fragility test
• insert RBCs into hypotonic solution. Normal RBCs (with adequate membrane) are able to intake liquid, but spherocytes (with less membrane) will lyse sooner.

Question 6

sickle cell anemia vs sickle cell trait:

-what do you see blood smear?

Answer 6

in SSA:

• sickled cells
• target cells (from loss of volume from dehydration b/c of damaged membranes)
• these are not seen in SS trait

Question 7

Hereditary spherocytosis

• tx
• what will look different or same on blood smear after tx?

Answer 7

• splenectomy. Spleen consuming spherocytes is the real problem, not the spherocytes themselves.
• After splenectomy, spherocytes will remain in blood. However, new presence of RBCs with Howell-Jolly bodies.

Question 8

Hereditary spherocytosis

what is the genetic problem, and what are the 3 proteins most affected?

Answer 8

Defect in tethering proteins that tether cytoskeleton to membrane of RBC. most commonly:

1. ankyrin
2. spectrin
3. band 3

Question 9

Acute chest syndrome

• what is this, how does it present
• what is the most common cause

Answer 9

• sickle cell anemia, complication of vaso-occlusion of pulmonary microcirculation. (most common cause of death in adults)
• presents with chest pain, SOB, lung infiltrates.
• pneumonia is most common cause. Pneumonia causes inflammation, so vasodilation, which slows the passage of blood. decreased RBC transit time increases incidence of deoxygenated RBCs, acidemia, and dehydration, which all conspire to increase sickling, which vaso-occludes the lung.

Question 9

Sickle cell anemia pt with proteinuria and hematuria:

what is happening?

Answer 9

-Renal papillary necrosis from vaso-occlusion

Question 10

Sickle cell anemia

-complications, divided into 2 categories

Answer 10

1. complications from RBC membrane damage
2. complications from vaso-occlusion of sickling

Question 12

MCHC

Answer 12

lab test: mean corpuscular Hb concentration

Hb concentration is higher in spherocytosis b/c RBCs have less membrane but same amount of Hb.

Question 13

Sickle cell anemia pt with pneumonia.

Fear what?

Answer 13

Fear onset of acute chest syndrome, which can be fatal

Question 14

blood smear: you see RBCs without central pallor

-what is this?

Answer 14

Spherocytes

Question 15

Hereditary spherocytosis

-how do RBCs become spherical?

Answer 15

-defect in tethering proteins means RBC continuously forms blebs of membrane on its surface. These blebs are removed by the spleen, resulting in RBCs with decreasing membrane, which is not enough membrane to allow RBC to be biconcave.

Question 16

Sickle cell anemia

• Why do RBCs sickle and when?
• when is there increased risk of sickling? (3 reasons)

Answer 16

The mutated beta chains means that the Hb produced is HbS, not HbA.

HbS polymerizes when deoxygenated, leading to sickled cells.

Increased sickling occurs with:

1. hypoxemia
2. dehydration
3. acidosis

Question 17

What infections is the spleen required to protect the body from? why?

Answer 17

Encapsulated organisms, eg S pneumo and H influenzae

-spleen is location of macrophages that eat bacteria that are opsonized with IgG or C3b. This is required to kill encapsulated bacteria

Question 17

Sickle cell anemia pt:

-what do you feel on abdominal exam?

Answer 17

• hepatomegaly (from extramedullary hematopoeisis)
• no splenomegaly (autosplenectomy)

Question 19

Sickle cell anemia

-why tx with hydroxyurea?

Answer 19

• hydroxyurea increases production of HbF, which is protective from sickling.
• mech unknown

Question 20

Sickle cell anemia

-how can it affect the bone? (3)

Answer 20

1. bone marrow expansion (from erythroid hyperplasia, in response to anemia). This leads to crewcut skull and chipmunk facies
2. Dactylitis–vaso-occlusion of bones in hands, feet
3. osteomyelitis from salmonella

Question 21

Pt with sickle cell anemia has chest pain

-suspect what?

Answer 21

-suspect acute chest syndrome

Question 22

Sickle cell anemia: complications due to RBC membrane damage (3 categories and their symptoms) -why is RBC membrane damaged in first place?

Answer 22

- RBC membrane damage when cells sickle and de-sickle while passing through microcirculation. 1. Extravascular hemolysis (predominant)--RBCs with membrane damage are consumed by macrophages in reticuloendothelial system. - anemia, jaundice, risk for bilirubin stones 2. Intravascular hemolysis--damaged RBCs dehydrate and hemolyze - target cells (from dehydration) - decreased haptoglobin (bind to free Hb) 3. Bone marrow expansion (erythroid hyperplasia) - 'crew cut' skull, 'chipmunk' facies - hepatomegaly from extramedullary hematopoeisis (remember autosplenectomy) - risk of aplastic crisis from parvovirus B19

Question 23

Hereditary spherocytosis - what do you see on blood smear? - lab findings of RDW and MCHC? why?

Answer 23

- spherocytes (loss of central pallor) - high RDW (spherocytes are at different stages of membrane loss) - high MCHC (mean corpuscular Hb concentration) b/c higher concentration of Hb.

Question 25

blood smear: you see RBCs with framents of nuclear material -what is this? when would you see these?

Answer 25

These are Howell-Jolly bodies in RBCs. You see these when the spleen is missing or not functioning. -the spleen normally removes RBCs that have abnormalities

Question 27

Hereditary spherocytosis -why is there anemia?

Answer 27

Spherocytes are consumed by macrophages in the spleen b/c they are less able to maneuver through splenic sinusoids. Loss of RBCs.

Question 28

Target cell -mech

Answer 28

-loss of cell volume, but no loss of membrane. Can be dehydration, can be Hb loss. ('basketball that loses air')

Question 30

Sickle cell anemia -what happens to the spleen? what are the complications (2)?

Answer 30

-autosplenectomy, b/c of vaso-occlusion. (shrunken, fibrotic spleen) 1 increased risk of infection from encapsulated organisms (S pneumo, H influenzae) 2. increased risk of Salmonella osteomyelitis - also, Howell-Jolly bodies in RBCs

Question 31

Pt with Sickle cell anemia -what might you see in the pt's hands?

Answer 31

- Swollen hands/feet (dactylitis) - caused by vaso-occlusion of bones, common in infants

Question 32

Sickle cell trait -symptoms

Answer 32

- generally asymptomatic b/c no polymerization of Hb - however, exception is the renal medulla b/c of its high hypoxia and hypertonicity. - microinfarcts occur in renal medulla, leading to microscopic hematuria and eventually, decreased ability to concentrate urine.

Question 33

Sickle cell gene: -main population, what %

Answer 33

gene carried by 10% of africans

Question 34

What vaccinations should kids with sickle cell anemia get? why?

Answer 34

- pneumococcal, and Hib vaccines. - both are encapsulated bacteria--autosplenectomy means decreased protection from them. Spleen is required for macrophages to eat bacteria that are opsonized with IgG or C3b. Encapsulated bacteria must be killed this way.

Question 35

Sickle cell anemia - when does newborn present with disease? - what is the classic sign in infants?

Answer 35

- presents several months after birth, after losing protective HbF. - classic presentation: Infant with dactylitis (swollen hands, feet from vaso-occlusive infarcts in bones)